(2-Aminoethoxy)(tert-butyl)dimethylsilane → (S)-N1-(2-(tert-butyldimethylsilyloxy)ethyl)-3-methyl-N2-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)butane-1,2-diamine

HRID 539016Notes

Reaction equation

HRID 539016 reaction equation
[CH3:1][CH:2]([CH3:35])[C@H:3]([NH:6][C:7]1[CH:12]=[CH:11][N:10]2[N:13]=[CH:14][C:15]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:24]=[CH:25][N:26]=4)=[CH:18][CH:17]=3)=[C:9]2[N:8]=1)[CH:4]=O.[Si:36]([O:43][CH2:44][CH2:45][NH2:46])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C1COCC1>[Si:36]([O:43][CH2:44][CH2:45][NH:46][CH2:4][C@@H:3]([NH:6][C:7]1[CH:12]=[CH:11][N:10]2[N:13]=[CH:14][C:15]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])[CH:24]=[CH:25][N:26]=4)=[CH:18][CH:17]=3)=[C:9]2[N:8]=1)[CH:2]([CH3:35])[CH3:1])([C:39]([CH3:41])([CH3:42])[CH3:40])([CH3:38])[CH3:37]

Participants

6

Reactant 3

HCID 529218(2-Aminoethoxy)(tert-butyl)dimethylsilaneHCID 5049666Sodium triacetoxyborohydrideHCID 86667823(S)-3-methyl-2-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-ylamino)butanal

Product 1

HCID 68088943(S)-N1-(2-(tert-butyldimethylsilyloxy)ethyl)-3-methyl-N2-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)butane-1,2-diamine

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-3-methyl-2-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-ylamino)butanal (27 mg, 0.055 mmol) in DCE (1 mL) was added a solution of 2-(tert-butyldimethylsilyloxy)ethanamine (29 mg, 0.17 mmol) in THF (0.2 mL). The reaction was allowed to stir at ambient temperature for 15 minutes, at which point Na(OAc)3BH was added and the reaction allowed to stir at ambient temperature for 2 hours. The reaction mixture was partitioned between saturated aqueous NaHCO3 and dichloromethane. The aqueous layer was extracted with dichloromethane. The combined extracts were washed with brine, dried and concentrated to give (S)—N1-(2-(tert-butyldimethylsilyloxy)ethyl)-3-methyl-N2-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)butane-1,2-diamine. The crude was used in the next step without further purification. LCMS (APCI+) m/z 650.9 [M+H]+.

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 and dichloromethane
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washThe combined extracts were washed with brine
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-af9745d036514735b53843d350443961
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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